CN107252382B

CN107252382B - Method, surgical kit and device for treating glaucoma

Info

Publication number: CN107252382B
Application number: CN201710293186.8A
Authority: CN
Inventors: L.平楚克
Original assignee: Innfocus Inc
Current assignee: Innfocus Inc
Priority date: 2012-01-12
Filing date: 2013-01-10
Publication date: 2020-04-10
Anticipated expiration: 2033-01-10
Also published as: US9101444B2; JP2020014952A; US10596036B2; DK3329884T3; EP2802300A2; AU2013240553A1; PL3329884T3; EP2802300B1; EP2802300A4; US20180344525A1; ES2887022T3; DK2802300T3; CN104168863A; EP3329884B1; EP3919030B1; KR20140120906A; WO2013147978A3; CA2859921A1; US9889042B2; PL2802300T3

Abstract

A surgical kit includes at least one instrument and at least one implant device. The instrument has a needle body for forming a surgical pathway through ocular tissue. The device includes a flexible tube defining a conduit for transferring aqueous humor, the flexible tube having an outer surface with a maximum cross-sectional dimension that is less than a maximum cross-sectional dimension of the needle body. The device incorporates a sealing means comprising at least one element defining a maximum cross-sectional dimension greater than the maximum cross-sectional dimension of the needle and being operably disposed within the surgical pathway and forming a seal between the surrounding ocular tissue and the element(s) and securing the device in the surgical pathway. The kit (and apparatus thereof) may be used as part of a surgical procedure to transfer aqueous humor to a space formed in ocular tissue.

Description

Method, surgical kit and device for treating glaucoma

The application is a divisional application of a PCT patent application (the Chinese national application number is 201380005419.X, the international application number is PCT/US2013/020920, and the invention name is 'method, surgical operation kit and device for treating glaucoma') which is submitted in 2013, 1 month and 10 days and enters the Chinese national stage.

Technical Field

The present invention relates to surgical treatment of glaucoma. More particularly, the present invention relates to medical devices and materials for transferring aqueous humor out of the anterior chamber through a surgically implanted conduit passageway.

Background

Glaucoma is a progressive ocular disease that manifests itself by elevated intraocular pressure ("IOP"). High pressure develops in the eye due to reduced outflow of aqueous humor. In open angle glaucoma, impaired outflow is caused by abnormalities in the drainage system of the anterior chamber. In closed angle glaucoma, impaired outflow is caused by impaired entry of aqueous humor into the drainage system. If the pressure within the eye is still high enough for a sufficiently long period of time, a loss of overall vision occurs. Thus, glaucoma is the leading cause of preventable blindness.

As shown in FIG. 1, eye 10 is a hollow structure in which anterior chamber 20 contains a clear fluid called an aqueous humor. The aqueous humor is formed by the ciliary body 12 near the posterior chamber 9 of the eye. Fluid produced at a fairly constant rate then passes around lens 14 through the pupillary opening in iris 18 and into anterior chamber 20. Once in anterior chamber 20, fluid exits eye 10 via two different routes. In the uveoscleral route, fluid seeps between the muscle fibers of the ciliary body 12. This route accounts for approximately ten percent of human aqueous outflow. The primary pathway of aqueous outflow in humans is through the microtubule route, which involves the trabecular network (not shown) and Schlemm's canal 24.

The network of trabeculae and schlemm's canal 24 are located at the junction between the iris 17 and the sclera 26. This junction, typically referred to as a corner, is designated 28. The trabecular network is a wedge-shaped structure that extends around the circumference of the eye. It consists of collagen beams arranged in a three-dimensional mesh-like structure. The beam is lined with a monolayer of cells called trabecular cells. The space between the collagen beams is filled with extracellular material, which is produced by trabecular cells. These cells also produce enzymes that degrade extracellular material. Schlemm's canal 24 is disposed adjacent to the trabecular network. The outer wall of the trabecular network coincides with the inner wall of Schlemm's canal 24. The antrum venosus 24 is a tubular structure that extends around the circumference of the cornea. In adults, schlemm's canal is considered to be divided by a septum into a series of independent, non-exiting channels. The aqueous humor fluid travels through the spaces between the trabeculae of the trabecular network, across the inner walls of schlemm's canal 24 into the channels, through a series of collection channels draining from schlemm's canal 24, and into the schlemm's venous system (not shown).

The tough outer membrane called the sclera 26 covers the entire eye 10 except for the portion covered by the cornea 34, which cornea 34 is a thin transparent membrane that covers the pupil opening and iris 18. The cornea 34 is incorporated into the sclera 26 at a junction known as the limbus 32. A portion of the sclera 26 is covered by a thin tissue known as Tenon's membrane 36 (also known as the Tenon's capsule) that envelops the eyeball from the optic nerve (not shown) to the ciliary body region. Near its anterior portion, tenon's capsule 36 blends into conjunctiva 30 where it attaches to the ciliary region of the eye, as shown.

In normal patients, aqueous humor production is equal to aqueous humor outflow, and intraocular pressure is still fairly constant (typically in the range of 8 to 18 mmHg). In glaucoma, there is an abnormal resistance to aqueous humor outflow, which manifests itself as increased IOP. Tonometry is a measurement of IOP. In primary open angle glaucoma, which is the most common form of glaucoma, abnormal resistance is believed to be along the outer aspect of the trabecular network and the inner wall of schlemm's canal 24. Primary open angle glaucoma accounts for approximately eighty-five percent of all glaucomas. Other forms of glaucoma, such as angle-closure glaucoma and secondary glaucoma, also involve reduced aqueous humor outflow through the microtubule pathway, but increased resistance results from other causes, such as mechanical obstruction, inflammatory debris, cellular obstruction, and the like.

As the resistance increases, aqueous humor accumulates because it cannot exit fast enough. As aqueous humor accumulates, IOP in the eye increases. Increased IOP compresses axons in the optic nerve and may also compromise the vascular junction with the optic nerve. The optic nerve carries vision from the eye to the brain. Some eyes appear to be more sensitive to damage from excessive IOP than others. Although research is being investigated as a means to protect nerves from high pressure, the currently available therapeutic approach in glaucoma is to reduce intraocular pressure.

Clinical treatment of glaucoma is typically performed in a step-wise fashion. Drug treatment is usually the first treatment option. These medications, administered topically or orally, act therapeutically to reduce aqueous humor production, or they act to increase outflow. If one medication fails, the patient is typically given a second medication, and then a third and fourth. Glaucoma patients are usually treated with four separate medications. Currently available drug therapies have a number of serious side effects, including: congestive heart failure, respiratory distress, hypertension, depression, kidney stones, aplastic anemia, sexual dysfunction, and death. In addition, preservatives in various medical treatments are known to cause damage to endothelial cells under the cornea, which can manifest as opacification of the cornea. In addition, preservatives can also alter the properties of the conjunctiva, which can lead to additional filtration problems. Compliance with drug therapy is also a major problem, where it is estimated that more than half of glaucoma patients do not follow their correct dosage plan, which can lead to progressive loss of vision.

Laser trabeculoplasty is typically performed when drug therapy fails to sufficiently lower IOP. In laser trabeculoplasty, thermal energy from a laser is applied to many non-contiguous points in a trabecular network. It is believed that the laser energy promotes the metabolism of the trabecular cells in some way and alters the cellular material in the trabecular network. In a larger percentage of patients, aqueous humor outflow is enhanced and IOP is reduced. However, the effect does not usually last long and a significant percentage of patients develop elevated IOP within a few years after treatment. Laser trabeculoplasty treatments are typically not repeatable. Furthermore, laser trabeculoplasty is not an effective treatment for primary open angle glaucoma in patients below fifty years of age, nor is it effective for angle-closure glaucoma and many secondary glaucomas.

If laser trabeculoplasty does not sufficiently lower IOP, open surgery (typically referred to as filtration surgery) is performed. The most commonly performed dissection procedure is drapery resection. The drape resection procedure involves cutting a "flap" in the sclera, and then punching a hole from within the wall of the flap into the anterior chamber, which allows fluid to drain from the anterior chamber into the flap, out the "flap" of the flap, and then into the bleb (blister formation) under the conjunctiva, thereby lowering IOP. The suture is placed under controlled tension to keep the door covering the door closed sufficiently to control IOP and avoid under-pressure (i.e., low IOP). Correct performance of the procedure is relatively difficult and has a high level of long-term complications. Additional interventions typically need to be performed to adjust the tension in the suture to further control IOP.

When the trabeculectomy has not successfully reduced eye pressure, the next and often final step is a surgical procedure that implants a Glaucoma Drainage Implant (GDI) that bypasses aqueous humor from the anterior chamber to control IOP. One such GDI, as shown in U.S. patent 6,050,970 to Baerveldt, is a drain tube that is attached at one end to a plastic panel. The drainage tube comprises a silicone rubber bypass having an outer diameter between 1.0 and 3.0 French; preferably, it has an inner diameter of 0.3mm and an outer diameter of 0.6mm (1.8 French). The Baerveldt tube is implanted by first making an incision in the conjunctiva 30, exposing the sclera 26, and dissecting the natural plane between the sclera and conjunctiva/tenon's capsule down to slightly beyond the equator. The plastic plate is sutured posteriorly to the surface of the sclera, usually above the equator. A full-thickness hole is typically made into the eye below the limbus 32 using a needle. The tube is inserted into the eye through the needle tract. The outer portion of the tube is covered by cadaveric sclera or other equivalent tissue to prevent erosion thereof through the conjunctiva. The conjunctiva 30 is replaced and the incision is tightly closed. With this bypass device, aqueous humor drains out of the anterior chamber through the tube and along the surface of the plate and into a bubble, wherein the bubble is defined as a thin layer of connective tissue encapsulating the plate and tube. The plates typically have a large surface area, which may be as large as 20mm in diameter, in order to wick and disperse fluid. Once the fluid accumulates in the bleb, it can be absorbed through the tissues of the bleb and enter the venous system of the sclera and to the surface of the eye, where it can evaporate or collect in the lacrimal gland. These plates are typically made of silicone rubber, which eventually becomes encapsulated by the connective tissue of the bubble. These large package boards are irritating to some patients.

Some of the currently approved GDIs include valves for tubes that enter the anterior chamber of the eye in order to control IOP and avoid hypotony. In addition, many GDIs, including the Baerveldt valves described above, tie their tubes to prevent too low a pressure in the acute phase before the capsule forms around the device. The ligated suture is then cleaved using a laser or dissolved within a month.

Current GDIs have an effective half-life of two to five years from implantation before the second, third or fourth GDIs are needed. Due to the bulky size of current GDIs, there is room for only three devices in the eye; the fourth device is rarely implanted. The problems associated with contemporary GDI are:

eye movement impairment and resulting diplopia (double images).

Hypotony (low IOP that can lead to retinal detachment).

Erosion and infection of the conjunctiva, and the associated high cost of using cadaveric sclera to prevent erosion. In addition, cadaveric sclera is difficult to obtain outside the united states, and several religious professions do not allow for the use of cadaveric tissue in vivo.

The tight encapsulation of the plate prevents proper filtration of the fluid and results in poor IOP control.

The difficulty in performing drape resection and GDI and their associated morbidity has led to the development of U.S. patent 7,431,709; 7,594,899, respectively; and 7,837,644; these patents are commonly assigned to the assignee of the present invention and are incorporated herein by reference in their entirety.

Disclosure of Invention

In one embodiment, a kit for treating glaucoma is provided that includes at least one handpiece, and at least one aqueous humor drainage device. The handpiece has a needle body that is inserted through eye tissue into the anterior chamber of the eye to define a passageway through the eye tissue to the anterior chamber. It is also contemplated that the portal through the eye tissue may be selectively widened by puncturing or by manipulating the tip of the needle to better accommodate the aqueous humor drainage device. The needle body has a maximum cross-sectional dimension (e.g., diameter D1 of fig. 5) along its length.

The aqueous humor drainage device includes a flexible tube defining a conduit for transferring aqueous humor from the anterior chamber. The tube has a proximal end and a distal end opposite each other. The distal end may have a tapered profile that facilitates insertion into a passage formed by the needle body that leads to the anterior chamber. The outer surface of the tube has a maximum cross-sectional dimension (e.g., outer diameter D2 of fig. 7) that is less than the maximum cross-sectional dimension of the needle body (e.g., diameter D1 of fig. 5). The apparatus also incorporates sealing means comprising at least one element spaced from the proximal and distal ends of the tube and extending radially outwardly beyond the outer surface of the tube. The element(s) define a maximum cross-sectional size that is greater than the maximum cross-sectional size of the needle (e.g., outer diameter D1 of fig. 5). The element(s) are operably disposed within the passage defined by the needle body and their relative sizes cause surrounding ocular tissue to directly contact the element(s) so as to form a seal between the surrounding tissue and the element(s). The seal surrounds the entire peripheral perimeter of the device defined by the element(s), and the seal prevents leakage of aqueous humor through the space between the tube and the surrounding ocular tissue. The element(s) of the sealing means also serve to fix the device in place in the passageway and minimize migration of the device in both the proximal and distal directions. The maximum cross-sectional diameter of the element(s) of the sealing device is defined by at least one blunt surface to facilitate sealing.

In one embodiment, the element(s) of the sealing means are realized by two tabs, which are arranged opposite each other on opposite sides of the tube. The two tabs may be generally planar in form and lie in a common plane extending transversely to the central axis of the tube. The substantially coplanar configuration of the tabs minimizes the profile of the device to reduce erosion and migration of the device. The two tabs may be mirror images of each other reflected about the central axis of the tube. The outer edge of the tab may have a tapered profile facing the distal end of the tube. The tapered profile facilitates the introduction of the tab into the passage formed by the needle body. The tabs may have a profile that tapers in a radial direction across the central axis of the tube (i.e., in the direction of the common plane of the two tabs).

In one embodiment, the instruments of the kit (including at least one hand-held instrument and at least one aqueous humor drainage device) are housed in one or more enclosures that provide easy access to the surgeon of the instrument when desired. The enclosure(s) may be realized from a suitable material, such as a thermoplastic, that is inexpensive and easy to dispose of for a single use. Other materials suitable for non-disposable applications (such as stainless steel, etc.) may also be used.

The insert may be used to deploy the device into a passage formed by the needle that leads to the anterior chamber. The insert may be made of a material similar to that of us patent 7,431,7091; 7,594,899, respectively; and 7,837,644, wherein one or both of the notches receive a tab of the device. Alternatively, the insert may be implemented with a stylet and/or trocar device as described below. In such embodiments, the insert may be part of a kit of appliances received in the enclosure.

In another embodiment, one or more elements of the kit may be used as part of a surgical procedure to transfer aqueous humor to a pocket area formed in ocular tissue (such as a pocket formed between the conjunctiva-sclera and tenon's capsule).

Drawings

Fig. 1 is a diagram showing anatomical details of a human eye.

Figure 2 is a schematic view of an embodiment of a handpiece for defining a surgical access through tissue to the anterior chamber of an eye.

Figure 3 is a perspective view of an embodiment of an aqueous humor drainage device to drain aqueous humor from the anterior chamber of an eye.

Fig. 4 is a perspective view of an embodiment of a surgical kit enclosure.

Fig. 5 is a side view of an exemplary embodiment of a needle body that is part of the handpiece of fig. 2.

Fig. 6 is a top view of an exemplary embodiment of the aqueous humor drainage device of fig. 3.

Fig. 7 is a side view of an exemplary embodiment of the aqueous humor drainage device of fig. 3.

Figures 8-11 are perspective views of different embodiments of aqueous humor drainage devices.

Fig. 12A-12D are cross-sectional schematic views of different embodiments of aqueous humor drainage devices, showing the maximum sized cross-sectional profile of the sealing tabs of the respective embodiments.

Figure 13A is a top view of an embodiment of an aqueous humor drainage device.

FIG. 13B is a schematic cross-sectional view of the aqueous humor drain of FIG. 13A through the cross-section labeled 13B-13B, showing the circular cross-sectional profile of the sealing tabs of the aqueous humor drain.

Figure 14A is a top view of an embodiment of an aqueous humor drainage device.

Figure 14B is a cross-sectional schematic view of the aqueous humor drain of figure 14A through the cross-section designated 14B-14B, showing the rectangular cross-sectional profile defined by the sealing tabs of the aqueous humor drain.

Fig. 15 is a diagram illustrating the aqueous humor drainage device of fig. 3 implanted in an eye to bypass aqueous humor from the anterior chamber to a space between tenon's capsule and the sclera of the eye.

Fig. 16 is a schematic diagram illustrating an embodiment of a stylet used to position an aqueous humor drainage device and an aqueous humor drainage device.

Fig. 17 is a schematic diagram illustrating another embodiment of a stylet for positioning an aqueous humor drainage device and an aqueous humor drainage device.

Figure 18A is a schematic view of an embodiment of a blade for use in a surgical method for treating elevated intraocular pressure, the blade for defining a passageway through tissue and in communication with an anterior chamber of an eye.

Fig. 18B is an enlarged view of the distal end of the knife of fig. 18A.

Figure 18C is a schematic view of an embodiment of a hand-held instrument for use in a surgical method for treating elevated intraocular pressure, the instrument for defining a passageway through tissue and in communication with the anterior chamber of an eye.

Fig. 19 is a side view of an embodiment of a trocar device inserted into a passageway through tissue and in communication with an anterior chamber of an eye for use in a surgical method for treating elevated intraocular pressure, and the trocar device receiving a tube of an aqueous humor drainage device for inserting the tube of the aqueous humor drainage device into the passageway.

Fig. 20A-20E illustrate the functionality of the trocar device of fig. 19 in an exemplary surgical method.

Fig. 21 is a side view of an alternative embodiment of a trocar device for use in a surgical method for treating elevated intraocular pressure, the trocar device being inserted into a passageway through tissue and in communication with an anterior chamber of an eye, and the trocar device receiving a tube of an aqueous humor drainage device for inserting the tube of the aqueous humor drainage device into the passageway.

Fig. 22A-22D illustrate the function of the trocar device of fig. 21 in an exemplary surgical method.

Detailed Description

As used herein, the term "distal" is generally defined as a direction along the patient's eye, or away from the user of the system/apparatus/device. Conversely, "proximal" generally means in a direction away from the patient's eye or toward the user of the system/apparatus/device.

Turning now to fig. 2 and 3, an embodiment of a kit for treating glaucoma is shown that includes at least one handpiece 101 (fig. 2) and at least one aqueous humor drainage device 201 (fig. 3). The instrument 101 has a needle 103 that is inserted into the anterior chamber 20 (fig. 1) of the eye via eye tissue to define a passageway to the anterior chamber 20 via the tissue. The needle body 103 has a maximum cross-sectional dimension (e.g., diameter D1 of fig. 5) along its length. The proximal end of the needle 103 is rigidly coupled to the hub 105. Handle 107 is rigidly coupled to bushing 105. The handle 107 is grasped by the surgeon's fingers for manipulating the needle body 103 as desired. A needle cover 109 may extend over the needle body 103 for safety. The needle body 103 may have a hollow bore (or possibly a solid bore). The hub 105 and handle 107 may be implemented by a syringe body that includes a plunger that fits within a tube, as is well known. The solution can be loaded into the tube and pumped through the hollow bore needle 103 by manual manipulation of the plunger. In addition, the needle body can be bent into a more desirable shape to accurately place the needle tubing, especially when the patient's nose blocks the needle shaft.

The aqueous humor drainage device 201 includes a flexible tube 203 that defines a conduit 205 for transferring aqueous humor from the anterior chamber 20. The tube 203 has a proximal end 207 and a distal end 209 opposite each other. The distal end 209 may have a tapered profile that facilitates insertion into a passage leading to the anterior chamber 20 formed by the needle body 103. The outer surface 211 of the tube has a maximum cross-sectional dimension (e.g., outer diameter D2 of fig. 7) that is less than the maximum cross-sectional dimension of the needle body 103 (e.g., diameter D1 of fig. 5). The device 201 also includes first and second tabs or

fins

213A,213B spaced from the proximal and

distal ends

207, 209 of the tube 203. The

tabs

213A,213B extend radially outward beyond the outer surface 211 of the tube 203 opposite one another on opposite sides of the tube 203. The first tab 213A and the second tab 213B may be generally planar in form and lie in a common plane that extends transverse to the central axis of the tube 203, as best shown in fig. 3. The substantially coplanar configuration of

tabs

213A,213B minimizes the profile of the device when placed flat against the sclera of the eye to reduce erosion and migration. The first tab 213A and the second tab 213B may be mirror images of each other reflected about the central axis of the tube 203 as shown. Tab 213A defines an outer edge 215A and tab 213B defines an outer edge 215B. The maximum distance between the outer edge 215A and the outer edge 215B defines a maximum cross-sectional dimension that is greater than the maximum cross-sectional dimension of the needle body 103 (e.g., outer diameter D1 of fig. 5).

Tabs

213A,213B are operably disposed within the passage defined by needle body 103 and are sized to cause surrounding tissue to directly contact

tabs

213A,213B to form a seal between the surrounding tissue and

tabs

213A, 213B. The seal surrounds the entire circumferential perimeter of the device defined by

tabs

213A,213B and prevents aqueous humor from leaking through the space between tube 203 and the surrounding tissue. The needle-defined pathway may also be widened in the scleral area with a sharp knife and associated puncture. The widened portion may be formed before or after the needle-defined passage is formed.

Tabs

213A,213B deform in the passageway in response to forces exerted by surrounding tissue as they are inserted into the passageway, and/or the surrounding tissue may deform (by compressing/stretching/thinning) as

tabs

213A,213B are inserted into the passageway. Such deformation is controlled by the maximum cross-sectional size of

tabs

213A,213B with respect to the cross-sectional size of the passage (e.g., formed by needle 103 or a puncture), and the stiffness of the material of

tabs

213A, 213B. The

tabs

213A,213B also serve to secure the device 201 in place in the passageway and minimize migration of the device 201 in both the proximal and distal directions.

The outer edges 215A,215B of the

tabs

213A,213B may have a tapered profile facing the distal end 209 as best shown on fig. 3. The tapered profile facilitates the introduction of

tabs

213A,213B into the passage formed by needle body 103.

The

tabs

213A,213B may have respective profiles that taper in a radial direction (i.e., in the direction of the common plane of the tabs) that is transverse to and away from the central axis of the tube 203, as best shown in fig. 3.

The outer surface 211 of the tube 203 has a maximum cross-sectional dimension (e.g., outer diameter D2) that is less than the maximum cross-sectional dimension of the needle body 103. For example, for a needle body 103 having a maximum cross-sectional dimension of 0.4mm, the outer surface 211 may have an outer diameter D2 that is less than 0.4mm (such as about 0.35 mm). In one embodiment, the conduit 205 of the tube 203 is a simple constant diameter lumen having a diameter in a range between 0.05mm and 0.15 mm. This small tube diameter restricts aqueous humor flow through the tube 203 and provides control of IOP without the need for a one-way valve or other structure (such as a filter) that restricts aqueous humor flow through the tube. More specifically, the diameter of conduit 205 alone controls the flow rate of aqueous humor through conduit 205, and thus the IOP of the patient. Suitable tubing diameters may vary from patient to patient depending on the rate of production of aqueous humor and the degree of obstruction of the patient's natural drainage pathway, and may therefore be selected by the physician as desired.

In one embodiment, an instrument comprising a kit of at least one hand-held instrument 101 (fig. 2) and at least one aqueous humor drainage device 201 (fig. 3) as described herein is housed in one or more enclosures, such as an instrument tray 401 as shown in fig. 4, which provides easy access to a surgeon of the instrument when desired. The ware tray 401 may be implemented from a suitable material (such as a thermoplastic) that is inexpensive and easily disposable for a single use. Other materials suitable for non-disposable applications (such as stainless steel, etc.) may also be used. The kit may include a plurality of hand-held instruments 101 (fig. 2) having different diameter needles, and/or a plurality of aqueous humor drainage devices 201 (fig. 3) with different sized tube conduits and/or tabs (e.g., a plurality of devices 201 having different tab sizes corresponding to the varying needle diameters of the instruments 101 of the kit). Further, to achieve a stab cut, knives of different diameters (discussed below with respect to fig. 18A and 18B) may be included in the kit as well as the measurement device, the medication, the sponge to apply the medication, the measurement device, the marker, the syringe, the cleaning fluid, the trocar, the insert, and the like.

The insert may be used to deploy the device 201 into the passage formed by the needle 103 that leads to the anterior chamber 20. The insert may be implemented by apparatus similar to that described in us patents 7,431,709, 7,594,899 and 7,837,644, wherein one or both slots receive

tabs

213A,213B of device 201. Alternatively, the insert may be implemented with a stylet and/or trocar device as described below. In such embodiments, the insert may be part of a kit of appliances received in the tray 401.

Fig. 5 shows the dimensions of an exemplary embodiment of the needle body 103. In the exemplary embodiment, needle body 103 has an outer diameter D1 of 0.4mm (i.e., 27 gauge). Other suitable outer diameters D1 may range from 0.4mm (i.e., 27 gauge) to 0.635mm (i.e., 23 gauge). The needle body 103 may also be provided with a bend to a desired shape to allow the needle to be inserted into the eye at an angle that would interfere with the patient's nose if not bent.

Fig. 6 and 7 illustrate the size of an exemplary embodiment of an aqueous humor drainage device 201 for use with the needle 103 of fig. 5. The tube 203 has a length of 8.5 mm. The pipe 205 has a diameter of 0.07 mm. The outer surface 211 has a maximum cross-sectional diameter (diameter D2) of 0.35mm, which is smaller than the outer diameter D1 of the needle body 103.

Tabs

213A,213B are spaced 4.5mm from distal end 209 of tube 203 and 3mm from proximal end 207 of tube 203. The

tabs

213A,213B are generally planar in form and lie in a common plane that extends transverse to the central axis of the tube 203. The

tabs

213A,213B are mirror images of each other reflected about the central axis of the tube 203 as shown. The planar form of the first and

second tabs

213A,213B has a maximum thickness (i.e., the outer diameter D2 of the tube 203) of about 0.35mm, a longitudinal dimension of 1mm parallel to the central axis of the tube 203, and a maximum cross-sectional dimension between the edges 215A,215B of 1.1 mm. In other designs, the maximum cross-sectional dimension between edges 215A,215B may be in a range between 0.9mm and 1.5 mm. Such maximum cross-sectional dimension is significantly greater than the 0.4mm outer diameter D1 for the needle body 103 of fig. 5.

Figures 8 to 14B show alternative designs of the tabs of the implantable aqueous humor drainage device. In the design of fig. 8, tab 213A1,213B1 has a profile that tapers in a radial direction across the central axis of tube 203, with the tapered radial surface of the tab extending from flat feature 217. In the design of fig. 9, tabs 213A,213B2 are portions of triangular wedge-shaped body 219 disposed along the longitudinal extent of tube 203. Proximal walls 221A,221B of the wedge-shaped body 219 are oriented transverse to a central axis of the tube 203, which is intended to help reduce migration of the tube 203 in a proximal direction out of the passageway formed by the appliance 101. In the design of fig. 10, tab 213A3,213B3 has proximal walls 223A,223B oriented transverse to the central axis of tube 203, which are intended to help reduce migration of tube 203 in the proximal direction out of the passageway formed by instrument 101. In the design of fig. 11, tabs 213A4,213B4 each have a curved wedge-like form. In the design of fig. 12A, tabs 213A5,213B5 and tube 203 define a diamond-shaped cross-sectional profile with radiused corners (specifically, a diamond-shaped profile that tapers in a radial direction across and away from the central axis of tube 203). The tapered surface of tab 213A5,213B5 extends from the annular surface of tube 203 as shown. In the design of fig. 12B, tab 213A6,213B6 defines a rectangular cross-sectional profile with semi-circular ends as shown. Alternatively, tab 213A6,213B6 may define a rectangular cross-sectional profile having a semi-elliptical end. In the design of fig. 12C, tabs 213A7,213B7 define an elliptical cross-sectional profile whose boundaries are radially offset from and surround the annular surface of tube 203. In the design of fig. 12D, tabs 213A8,213B8 define a cross-sectional profile of a larger radius ellipse (compared to the elliptical profile of fig. 12C) whose boundaries are radially offset from and surround the annular surface of tube 203.

In the design of fig. 13A and 13B, cork-like tabs 213' are provided extending circumferentially beyond the annular surface of the tube 203. The cork tab 213' has a circular cross-sectional profile as is evident from the view of fig. 13B.

In the design of fig. 14A and 14B, a generally planar tab 213 "is provided extending circumferentially beyond the annular surface of the tube 203. The generally planar tabs 213 "have a rectangular cross-sectional profile as is evident from the view of fig. 14B.

The outer surface(s) of the tab(s) of the device 201 may be blunt with rounded features as shown, and thus avoid any sharp corners and edges. The blunt outer surface(s) of the tab(s) are particularly suitable for forming a seal against surrounding tissue as described herein.

In the design of fig. 11, the slits 225 are formed in the

tabs

213A,213B in such a way that the slits 225 intersect the lumen 205 of the aqueous humor drainage device 205. Slit 225 is positioned proximal to the portion of

tabs

213A,213B that forms a seal to the surrounding tissue (i.e., the blunt outer edges of

tabs

213A,213B at their greatest radial distance relative to the central axis of tube 203). The purpose of the gap 225 is twofold. First, the slit 225 may act as a pressure relief valve in the event that the lumen 205 of the aqueous humor drainage device 205 becomes occluded downstream due to tissue proliferation in the bleb. The elastomeric nature of the aqueous humor drainage device 205 allows the slit 225 to change to an open state when pressure builds within the lumen 205, wherein aqueous humor is released into the bubble, thereby reducing the pressure in the anterior chamber. A second advantage of the gap 225 is that the same purpose is intentionally achieved; i.e., pressure relief in the anterior chamber. To accomplish this release, the lumen 205 downstream of the gap 225 is sealed closed, forcing fluid to escape via the gap 225. The length and width of the gap 225 control the pressure at which the aqueous body escapes and may be tailored to prevent too low a pressure. The aqueous humor escapes via the slits 225 and flows proximally in the space between the surrounding tissue and the outer surface of the proximal portion of the tube 203. Fluid escaping through the slit 225 will pass through both the narrow lumen 205 of the distal portion of the tube 203 and the slit 225 to cause its pressure to drop. The circumferential annular leakage of aqueous humor in the space between the surrounding tissue and the outer surface of the distal portion of tube 203 is blocked by the seal formed by

tabs

213A, 213B. More specifically, the blunt outer edges of

tabs

213A,213B at their maximum radial offset relative to the central axis of tube 203 form seals with the surrounding tissue that block such circumferential annular leakage of aqueous humor.

The aqueous humor drainage device 201 can be formed of a homogenous polymeric material. In one embodiment, the homogeneous polymeric material is a polyolefin copolymer material having a triblock polymer backbone comprising polystyrene-polyisobutylene-polystyrene, which is referred to herein as "SIBS". SIBS may also be referred to as poly (styrene-b-isobutylene-b-styrene), where b represents a "block". High molecular weight Polyisobutylene (PIB) is a soft elastomeric material having a shore hardness of about 10A to 30A. When copolymerized with polystyrene, it can be made at a hardness in the range up to that of polystyrene, which has a shore hardness of 100D. Thus, depending on the relative amounts of styrene and isobutylene, the SIBS material may have a range from soft to 10 shore a hardness to hard to 100 shore D hardness. In this manner, the SIBS material may be adapted to have desired elastomeric and hardness qualities. In a preferred embodiment, the SIBS material of the aqueous humor drainage device tube 201 has a hardness less than 50 shore a and greater than 20 shore a. Details of SIBS materials are described in U.S. patent No. 5,741,331; 6,102,939 No; 6,197,240 No; 6,545,097, which are hereby incorporated by reference in their entirety. The SIBS material of the aqueous humor diversion device 201 can be polymerized under controlled means using carbocationic polymerization techniques, such as those described in U.S. patent nos. 4,276,394; 4,316,973 No; 4,342,849 No; 4,910,321 No; 4,929,683 No; U.S. Pat. No. 4,946,899; 5,066,730 No; 5,122,572 No; and those described in reference 34,640, each incorporated herein by reference in its entirety. The amount of styrene in the copolymer material is preferably between 16 mol% and 30 mol%, and most preferably between 20 mol% and 27 mol%. The styrene and isobutylene copolymer materials are preferably copolymerized in a solvent.

The alternative vitreous segment of styrene described above may be used to implement the aqueous humor drainage device 201. the vitreous segment provides a hardener component for the elastomeric polyisobutylene.

BAB or ABA (linear triblock),

b (AB) n or (BA) n (linear alternating block), or

X- (AB) n or X- (BA) n (including diblock, triblock, and other radial block copolymers), where a is an elastomeric polyolefin block, B is a thermoplastic block, n is a positive integer, and X is the starting seed molecule.

Such materials may be radial block copolymers (where n =3 or greater), or multi-dendritic block copolymers. In addition to the glassy segments, a crosslinking agent can be incorporated into the polymer to provide a thermally set version of SIBS. Exemplary polymers incorporating these crosslinking agents are described in detail in U.S. patent publication 20090124773, which is incorporated herein by reference in its entirety. These materials collectively belong to the polymeric materials referred to herein as SIBS materials.

Other polymeric materials may be used to provide the aqueous humor drainage device 201 according to the present invention. Exemplary materials are flexible materials that can conform to the surface of the eye and include, but are not limited to, silicone rubber, polyolefins (butyl rubber, polybutadiene, styrene-ethylene-propylene-butadiene, polyethylene, polypropylene, etc.), polyurethanes (polyether urethanes, polycarbonate urethanes, polyurethanes containing polyisobutylene or other polyolefin soft segments, etc.); acrylic acid (polyacrylate, poly (2-hydroxyethyl methacrylate), etc.), fluoropolymers (PTFE, ePTFE, fluorosilicone rubber, poly (-CH2-CF2) -etc.), polyamides, hydrogels, bio-based structures such as those comprising collagen, elastin, etc.; and mixtures of all of the above, and soft foams and porous polymeric materials may be used to implement the aqueous humor drainage device 201. The polymeric material should be biocompatible and biostable within the ocular environment.

The entire aqueous humor drain 201 can be formed as an integral part by molding a polymeric material. It is also contemplated that the polymeric material of the

tabs

213A,213B may be different than the polymeric material of the tube 203. This may be accomplished by insert molding techniques or other suitable thermoplastic forming techniques. The

tabs

213A,213B may be the same durometer as the tube 203, or they may be different from the tube 203. In one embodiment, the hardness of

tabs

213A,213B is in a range between 30 shore a and 80 shore a.

Turning now to fig. 15, an aqueous humor drainage device 201 is shown implanted such that its distal end 209 is positioned within the anterior chamber 20 of the eye and its proximal end 207 is positioned within a pocket 300 formed between tenon's capsule 36 and sclera 26 (fig. 1). Bag 300 defines an enclosed space between tenon's capsule 36 and sclera 26 (fig. 1). The conduit 205 of the aqueous humor drainage device 201 bypasses aqueous humor from the anterior chamber 20 to the bag 300, which forms a shallow bubble. The aqueous humor is absorbed into the adjacent tissue and ends up in the venous system of the eye or in the tear film, or once it reaches this, simply evaporates from the outside of the conjunctiva.

The pouch 300 may extend from a location at or near the limbus to the back of the eyeball adjacent to or beyond the equator of the eye. The pocket 300 may be defined by making an incision through the conjunctiva or tenon's capsule 36 to the scleral surface, and then dissecting and separating tenon's capsule 36 from the sclera 26 (fig. 1) over the area of the pocket 300. A pouch of this type is called a vault-based pouch if the hinge (hinge) from the pouch is in the vault of the eye. This type of pouch is called a limbal-based pouch if the hinge is located at an incision in the limbus and fornices. The distal end 209 of the aqueous humor drainage device 201 is inserted through the needle-formed passage, through the horn 28, to the anterior chamber 20 of the eye. Device 201 is further advanced into the passageway such that

tabs

213A,213B (only tab 213A is shown in fig. 15) are positioned within the passageway. The size of

tabs

213A,213B causes the surrounding tissue to directly contact

tabs

213A,213B to form a seal between the surrounding tissue and

tabs

213A,213B and prevents aqueous humor from leaking through the space between tube 203 and the surrounding tissue.

Tabs

213A,213B may deform in the passageway in response to forces applied by surrounding tissue as they are inserted into the passageway, and/or the surrounding tissue may deform (by stretching/thinning) as

tabs

213A,213B with respect to the cross-sectional size of the passage (as formed by needle body 103), and the hardness of the material of

tabs

213A, 213B. The

tabs

213A,213B also serve to secure the tube 203 in place in the passageway and minimize migration of the tube 203 in both the proximal and distal directions. After the device 201 is properly positioned, the pouch 300 is closed. A sponge, absorbent paper, or other suitable carrier loaded with an anti-proliferative agent may be placed within the pouch 300 prior to the pouch 300 being closed. For example, the antiproliferative agent may be oxytetracycline C or 5-fluorouracil or other antimetabolite or other suitable drug(s) or compound(s) that is released immediately or over a period of time and acts to minimize conjunctiva-sclera to tenon's capsule fibrosis, thereby maintaining the structure of the pouch 300 for an extended period of time. Alternatively, a collagen sponge or other space-filling structure or fluid may be placed in the bag to prevent conjunctiva/tenon's capsule to sclera healing. Aqueous fluid flows from the anterior chamber 20 through the conduit 205 of the device 203 and into the sealed bag 300. The sealed pouch 300 prevents bacteria from entering the device 201 and infecting the eye. The aqueous body leaving the device 201 and entering the sealed pouch 300 creates a very shallow bubble. The bubble fluid may be filtered into or evaporated from the tears through the conjunctiva 30 (fig. 1), and the fluid may be absorbed through the lymphatic system and capillaries penetrating the conjunctiva 30 (fig. 1). A portion of the aqueous humor contained in the bleb can potentially seep through the permeable sclera 26 and be absorbed by the choroidal capillaries.

The aqueous humor drainage device 201 can be implanted in the position shown in fig. 15 using the following method. The pouch 300 is made by dissecting the conjunctiva 30 using microscissors (Vannas scissors or the like) at the limbus 32 in the incision area of less than one quadrant, and dissecting and separating the tenon's capsule 36 a few millimeters (a vault-based flap) from the sclera 26. The edges of pouch 300 are then held at their center with a pair of toothed forceps, the closed ends of a pair of blunt scissors (e.g., Westcott or the like) are slowly pushed down toward the equator of the eye, and open to separate (delaminate) tenon's capsule 36 from sclera 26. Closing the scissors again; the tip is pushed further forward and reopened to separate a larger area of tenon's capsule 36. This process is repeated until the ends of the scissors are 17 to 20mm away from the limbus 32. The resulting bag 300 is larger at the equator base than at the limbal entrance.

The pocket 300 is formed near the limbus 32. The mark in the center of the middle of the conjunctival opening is made 2 to 3mm behind the limbus edge using a blunt caliper. Tissue ink may be used on the ends of the jaws to increase the contrast of the tissue marks. The hand-held instrument 101 with the needle 103 (fig. 1) is prepared and the tip of the needle 103 is positioned at the mark made on the sclera. The surgical access is adapted to connect the outer scleral wall to the anterior chamber by pushing the needle 103 in a plane such that the tip of the needle 103 enters the eye into the anterior chamber 20 via the angle 28. In this manner, the surgical pathway passes through the conjunctiva-sclera near angle 28 and into anterior chamber 20. The device 101 may be a syringe that holds a solution of a medicament, such as epinephrine or lidocaine. The surgeon may choose to dispense the solution from the syringe into anterior chamber 20 after introducing the distal end of syringe needle 103 into anterior chamber 20. After waiting some time (e.g., a few seconds), the needle 103 is slowly retracted. Aqueous humor drainage device 201 is inserted into the surgical pathway into the position shown in fig. 15, whereby distal end 209 enters anterior chamber 20 of the eye and

tabs

213A,213B are positioned within the surgical pathway. Prior to introducing the device 201 into the surgical pathway, the proximal end of the surgical pathway may be enlarged at the scleral surface by means of a stab cut with a sharp knife (such as the knife of fig. 18A and 18B described below), or by cutting an entry into the sclera with the sharp edge of the needle 103 as the needle 103 is retracted. This stab incision may facilitate introduction of

tabs

213A,213B of device 201 into a surgical pathway. Alternatively, the sharp knife is used to make a shallow slit or puncture into the sclera prior to making the surgical access. The needle is then inserted into the slit and the surgical pathway formed below the limbus. The

tabs

213A,213B are then rolled into the puncture wound as described above.

Tabs

213A,213B are sized to cause surrounding ocular tissue of the surgical pathway to directly contact

tabs

213A,213B to form a seal between the surrounding ocular tissue and

tabs

213A,213B and prevents aqueous humor from leaking through the space between tube 203 and the surrounding ocular tissue of the surgical pathway. The proximal end 207 of the tube 203 is positioned in the pouch 300 as shown in fig. 15. The aqueous humor drainage device 201 may be configured from an insert device similar to that described in U.S. patents 7,431,709, 7,594,899 and 7,837,644, wherein one or both slots receive

tabs

213A,213B of the device 201. Alternatively, the aqueous humor drainage device 201 may be inserted into the pathway using the oral needle 301 and/or trocar device 350 (or 410) as described below. The pouch 300 is then closed with stitches 304. Instead of sutures, bipolar diathermy coagulation, laser welding or adhesives (such as cyanoacrylate, fibrin glue, etc.) may be used to close the pouch body 300. In addition, the trocar may be used to facilitate placement of the aqueous humor drainage device through the needle passageway.

To minimize irritation and reduce surgical time, the bag 300 can also result from dissection of the conjunctiva at the limbus and, starting at one edge of the dissection, cuts back the conjunctival tissue by approximately 3mm, thus creating a flap gate. After forming a surgical pathway into the exposed sclera and through to the anterior chamber, device 201 is positioned in the surgical pathway with the proximal end of the device in pouch 300 as shown in fig. 12. The free edges of the conjunctiva 30 are then side-by-side beyond their original position by about 2mm and held in tension by coagulation with a single suture or a single laser weld or a single point bipolar diathermy or with a single point adhesive. The conjunctiva 30 is not treated along the limbus 32, but remains intact to prevent necrosis of the tissue causing fibrosis. The corneal-limbal epithelial cells will rapidly recover (1 hour or less) the injured limbus, sealing the conjunctival limbus.

A sponge, absorbent paper, or other suitable carrier carrying one or more therapeutic agents may be placed within the pouch 300 prior to the pouch 300 being closed. Such therapeutic agent(s) are released over time and minimize tenon's capsule to sclera fibrosis, thereby preventing re-lamination and closure of the alveolar space (the interior space of the closed pouch 300 surrounding the proximal end 207 of the tube 203). The therapeutic agent(s) may include cytostatic agents (i.e., antiproliferative agents that prevent or delay cell division, e.g., by inhibiting DNA replication, and/or by inhibiting spindle yarn formation, and/or inhibiting cell migration) or other agents that minimize fibrosis or blood clots. Examples of such therapeutic agents are described below.

Fig. 16 shows an aqueous humor drainage device 201 having a stylet 301 removably inserted into the lumen 205 of the proximal portion 209 of the device 201 to facilitate insertion of the device 201 into the pathway formed by the needle. The proximal end of the stylet 301 is bent in a pigtail configuration 302 to enable the surgeon to grasp the stylet 301 and remove it from the lumen 205 of the aqueous humor drainage device 201 once it is in place. Figure 17 shows another embodiment of a stylet 301 with a larger tube 303 crimped onto the proximal end of the stylet to facilitate grasping and removal.

Fig. 18A and 18B illustrate a handheld knife 340 that may be used to make a puncture in the sclera to further secure the elements of the aqueous humor drainage device 201 in the sclera. The diameter "a" of knife edge 341 is less than the maximum cross-sectional diameter of

tabs

213A,213B of device 201 in order to allow

tabs

213A,213B to slip fit into the puncture. The length b of the cutting edge 341 may be approximately the same size as the size a.

Fig. 18C shows an embodiment of a handpiece 342 including a distal needle 343 extending from a flat blade portion having

cutting surfaces

344A, 344B. The needle body 343 creates a passageway leading through the sclera and the cutting surfaces 344A,344B create a widened puncture wound in the sclera in one movement of the surgeon's hand.

When the needle body is removed from the needle forming passage, the needle passage may sometimes become oval (or collagen fibers that span the passage, or there is a bend in the passage), which makes it difficult to place the aqueous humor drainage device 201 through the passage. To facilitate placement of the aqueous humor drainage device 201 into the needle formed pathway through the sclera, a trocar 350 (fig. 19) may be provided that includes a catheter 352 having a ground notch 351. The catheter 352 is sized to receive the needle 103 and the tube 203 of the aqueous humor drainage device 201. The trocar 350 is placed over the needle 103 to provide the assembly 360 shown in fig. 20A. Fig. 20B to 20E illustrate the function of the trocar 350. As shown in fig. 20B, assembly 360 is inserted into the needle forming passageway through sclera 400. The needle body 103 is then removed from the assembly, leaving the trocar 350 in place, as shown in fig. 20C. As shown in fig. 20D, the aqueous humor drainage device 201 is then advanced through the trocar 350. The trocar 350 is then removed, leaving the aqueous humor drainage device 201 behind within the needle formed pathway, as shown in fig. 20E. The resilient nature of tube 203 of device 201 allows tube 203 to bend and deform such that it passes through notch 351 of trocar 350 when trocar 305 is removed. The position of aqueous humor drainage device 201 within the passageway can then be adjusted by the surgeon (e.g., by further inserting device 201 into the passageway) such that

tabs

213A,213B abut the tissue walls of the passageway and provide a seal between the tissue and device 201. In this position,

tabs

213A,213B also serve to secure the device in the passageway.

FIG. 21 shows another embodiment of trocar 410 including a catheter 412 having a notch 411, notch 411 being partially ground along catheter 412. The segments of the cover (e.g., tabs 413) of the milled notches remain integral with the tube as shown. The catheter 412 is sized to receive the needle 103 and the tube 203 of the aqueous humor drainage device 201. Trocar 410 is placed over needle 103 with bushing 415 abutting the proximal end of catheter 412 to provide the assembly shown in fig. 22A. Fig. 22B to 22D illustrate the function of the trocar 410. As shown in fig. 22B, the assembly is inserted into the needle forming passage through sclera 400. Abutment of catheter 412 against bushing 415 prevents trocar 410 from sliding back over the needle body as it is inserted through tissue. As shown in fig. 22C, the needle body 103 is removed from the trocar 410, which is facilitated by grasping the tab 413 with forceps as the needle 103 is pulled out of the trocar 410. Once the needle 102 is removed, the trocar 410 is cut at line 420 (e.g., with scissors) and the proximal portion of the catheter 412 with the tabs 413 is discarded as shown in fig. 22D. Next, the aqueous humor drainage device 201 is advanced through the remaining trocar portion 421 into the needle forming passageway in a manner similar to the method described above in connection with fig. 20D. The trocar portion 421 is then removed, leaving the aqueous humor drainage device 201 behind within the needle formed pathway, as shown in fig. 20E. The resilient nature of the tube 203 of the device 201 allows the tube 203 to bend and deform so that it passes through the slot 411 of the trocar portion 421 when the trocar portion 421 is removed. The position of aqueous humor drainage device 201 within the passageway can then be adjusted by the surgeon (e.g., by further inserting device 201 into the passageway) such that

tabs

213A,213B also serve to secure the device in the passageway.

Another embodiment contemplated by the present invention is to first form a needle channel below the limbus using a needle 103, then preload the tube 203 of the aqueous humor drainage device 201 into the

trocar

350 or 410, and then push the assembly through the needle channel. The trocar is then removed from the needle tract as explained above.

The trocar of fig. 19 and 21 may be made of a rigid thin hard material, preferably polyimide. Other materials that may play a role in this capacity are PEEK, peeek, polyurethane, polypropylene, high molecular weight polyethylene, nylon, fluoropolymers, and the like. Alternatively, the material forming the trocar may be made of metal (preferably a well-known metal used in medical devices, such as stainless steel, titanium, nitinol, etc.). The primary requirement is that the trocar not catch when it is inserted through tissue. The wall thickness of the trocar should be between 0.0002 "and 0.003"; preferably between 0.001 and 0.003 ". The inner diameter of the trocar should be equal to or greater than the diameter of the needle body 103; i.e. equal to or larger than the flexible tube 102 if inserted over the needle (if the trocar is preloaded with an aqueous humor drainage device).

The polymeric aqueous humor drainage device 201 (or portions thereof) may be loaded with one or more therapeutic agents that are released over time and minimize tenon's capsule to sclera fibrosis, thereby preventing re-lamination and closure of the alveolar space. The therapeutic agent(s) loaded into device 100 may include cytostatic agents (i.e., antiproliferative agents that prevent or delay cell division, for example, by inhibiting DNA replication, and/or by inhibiting spindle wire formation, and/or by inhibiting cell migration) or other agents that minimize fibrosis or blood clots. Examples of such therapeutic agents are as follows.

Representative examples of therapeutic agents include the following: visfatal, ranibizumab (rhuFab V2 AMD), combretastatin A4 prodrug, SnET2, H8, VEGF Trap, Cand5, LS 11(Taporfin Sodium), AdPEDF, Retinostat, integrin, Panzem, Retanane, anecortave acetate, VEGFR-1 mRNA, ARGENT cell-signaling technology, angiotensin II inhibitors, isotretinoin for blindness, Macugen (PEGylated aptamer), PTAMD, triopn, AK-1003, NX1838, avb3 and5 antagonists, Neovastat, Eos 200-F, and any other VEGF inhibitors.

Other therapeutic agents may be used, such as: doxycycline C, 5-fluorouracil, corticosteroid (corticosteroid triamcinolone acetonide is the most common), modified toxin, methotrexate, adriamycin, a radionuclide (e.g., such as disclosed in U.S. patent No. 4,897,255, which is incorporated herein by reference in its entirety), protein kinase inhibitors (including staurosporine, which is a protein kinase C inhibitor, and stimulators of production or activation of diindolalkaloids and TGF-beta, including tamoxifen and functionally equivalent derivatives, e.g., cytoplasmic, heparin, a compound capable of reducing the level or inactivation of lipoprotein lp (a) or its glycoprotein apolipoprotein (a)), a nitric oxide releasing compound (e.g., nitroglycerin) or an analog or functional equivalent thereof, paclitaxel or an analog or functional equivalent thereof (e.g., taxotere or Taxol-based formulations, the active ingredient of which is paclitaxel), inhibitors of specific enzymes (such as the ribozymes DNA topoisomerase II and DAN polymerase, RNA polymerase, adenylate uridylate cyclase), superoxide dismutase inhibitors, terminal transdeoxynucleotidyl transferase, reverse transcriptase, antisense oligonucleotides that inhibit cell proliferation, angiogenesis inhibitors (e.g., endostatin, angiostatin and squalamine), rapamycin, zotarolimus, cilastatin and frataxime and suramin, etc.

Other examples of therapeutic agents include amino acids or similar inhibitors, such as anti-, agonistic, or competitive or non-competitive inhibitors of cellular factors that can trigger cell proliferation, or pericytes (e.g., cytokines (e.g., intermediate leukokines, such as IL-1)), growth factors (e.g., PDGF, TGF- α or β, tumor necrosis factors, smooth muscle and endothelial derived growth factors, such as endothelin or FGF), homing receptors (e.g., platelets or leukocytes), and extracellular matrix receptors (e.g., integrins).

Representative examples of useful therapeutic agents in the class of agents that address cell proliferation include: a subfragment of heparin, triazolopyrimidine (e.g., trapidil, which is an antagonist of PDGF), lovastatin; and prostaglandin E1 or I2.

Several of the above and many additional therapeutic agents suitable for the practice of the present invention are disclosed in U.S. patent nos. 5,733,925 and 6,545,097, both of which are incorporated herein by reference in their entirety.

If desired, the therapeutic agent of interest may be provided simultaneously with the polymer, whereby the device 201 is achieved, for example, by adding it to the polymer melt during thermoplastic processing or by adding it to the polymer solution during solvent-based processing. Alternatively, the therapeutic agent may be provided after the device or device portion is formed. As an example of these embodiments, the therapeutic agent may be dissolved in a solvent that is compatible with both the device polymer and the therapeutic agent. Preferably, the device polymer is at most only slightly soluble in this solvent. Subsequently, the solution is contacted with the device or device portion such that the therapeutic agent is loaded (e.g., by leaching/diffusion) into the copolymer. For this purpose, the device or device parts may be immersed or dipped into a solution which may be applied to the device or component, for example by spraying, printing dip coating, immersion in a fluidized bed, or the like. The device or member can then be dried with the therapeutic agent retained therein.

In another alternative, the therapeutic agent may be disposed within a matrix comprising the polymer of device 201. The therapeutic agent may also be covalently, hydrogen bonded, or electrostatically bonded to the polymer of the device 201. As a specific example, a nitric oxide releasing functional group (such as S-nitroso-thiol) may be provided in connection with the polymer, or the polymer may be provided with a charged functional group to attach a therapeutic group with an oppositely charged functionality.

In yet another alternative embodiment, the therapeutic agent may be deposited onto one or more surfaces of the device 201 (or device portion). These surface(s) may then be covered with a coating of polymer (with or without additional therapeutic agent) as described above.

Thus, for purposes herein, when it is stated that a polymer is "loaded" with a therapeutic agent herein, it is meant that the therapeutic agent is associated with the polymer in a manner similar to or in a related manner to those described above.

In some cases, a bonding agent may be used to bond to the substrate. Examples of suitable materials for the binder in connection with the present invention include silanes, titanates, isocyanates, carboxyl groups, amides, amines, hydroxyacrylates (acryloxys), and epoxides, including certain polymers such as EVA, polyisobutylene, natural rubber, polyurethane, silicone coupling agents, ethylene and propylene oxide.

Also useful is a polymer (which may or may not contain a therapeutic agent) that coats the device 201 with an additional polymer layer (which may or may not contain a therapeutic agent). For example, the layer may serve as a boundary layer to retard diffusion of the therapeutic agent and prevent explosive phenomena, whereby many of the agent is released immediately upon exposure of the device or device portion to the implantation site. The material comprising the coating or boundary layer may or may not be the same polymer as the loaded polymer. For example, the barrier layer may also be a polymer or small molecule from the following classes: polycarboxylic acids, including polyacrylic acid; cellulosic polymers including cellulose acetate and cellulose nitrate; gelatin; polyvinylpyrrolidone; crosslinked polyvinylpyrrolidone; polyanhydrides including maleic anhydride polymers; a polyamide; polyvinyl alcohol; copolymers of ethylene monomers, such as EVA (ethylene vinyl acetate); a polyvinyl ether; a polyvinyl aromatic compound; polyethylene oxide; an aminopolysaccharide; a polysaccharide; polyesters including polyethylene terephthalate; polyacrylamide; a polyether; polyether sulfone; a polycarbonate; polyhydroxyl groups including polypropylene, polyethylene and high molecular weight polyethylene; halogenated polyhydroxyl groups including polytetrafluoroethylene; a polyurethane; a poly-n-ester; polypeptides, including proteins; a silicone resin; a siloxane polymer; polylactic acid; polyglycolic acid; polycaprolactone; polyhydroxybutyrate valerate and mixtures and copolymers thereof; coatings from polymer dispersions, such as polyurethane dispersions (bayhdrol.rtm. etc.); fibrin; collagen and derivatives thereof; polysaccharides such as cellulose, starch, dextran, alginates and derivatives; and hyaluronic acid.

The above copolymers and mixtures are also contemplated.

The mixture can also be utilized to form the aqueous humor drainage device 201 (or device portion) by adding one or more of the above or other polymers to the block copolymer. Examples include the following:

the mixture can be formed with a homopolymer that can be mixed with one of the block copolymer phases. For example, polyphenylene ether can be mixed with the styrene block of a polystyrene-polyisobutylene-polystyrene copolymer. This will increase the strength of the molded part or coating made of polystyrene-polyisobutylene-polystyrene copolymer and polyphenylene ether.

The mixture may be made by adding a polymer or other copolymer that is not fully miscible with the blocks of the block copolymer. The added polymer or copolymer can be advantageous, for example, where it is compatible with another therapeutic agent, or it can alter the release rate of a therapeutic agent from a block copolymer (e.g., a polystyrene-polyisobutylene-polystyrene copolymer).

The mixture can be made using ingredients such as sugars (see above) that can leach out of the device 201 (or device portion), making the device or device member more porous, and controlling the release rate through the porous structure.

The release rate of the therapeutic agent from the therapeutic agent loaded polymer of the present invention can vary in a number of ways. Examples include:

the molecular weight of the block copolymer is varied.

The particular components selected for the elastomeric and thermoplastic portions of the block copolymer, as well as the relative amounts of these components, vary.

The type and relative amount of solvent used in processing the block copolymer is varied.

The porosity of the block copolymer is varied.

A boundary layer is provided over the block copolymer.

The block copolymer is mixed with other polymers or copolymers.

Furthermore, while it is seemingly desirable to provide control over the release of the therapeutic agent, e.g., as a rapid release (hours) or as a slow release (weeks), it may not be necessary to control the release of the therapeutic agent. In such embodiments, one or more of the therapeutic drug agents described herein (e.g., antiproliferative agents derived from doxycycline C or 5-fluorouracil) can be injected into the pouch 300 at the time of surgery.

Several embodiments of glaucoma implant devices, kits, and methods that migrate aqueous humor from the anterior chamber of the eye, and surgical methods associated therewith, have been described and illustrated herein. While particular embodiments of the invention have been described, it is not intended that the invention be limited thereto, as it is intended that the invention be as broad in scope as the art will allow and that the specification be read likewise.

Thus, while a particular method of fabrication has been disclosed, it will be understood that other methods of fabrication may be used. For example, because the copolymer materials described herein have thermoplastic properties, a variety of standard thermoplastic processing techniques can be used with the devices described herein. Such techniques include compression molding, injection molding, blow molding, spinning, vacuum forming and calendering, as well as extrusion into tubes and the like. Such devices may also be fabricated using solvent-based techniques involving solvent casting, spin coating, solvent spraying, dipping, fiber formation, inkjet techniques, and the like. Additionally, while it is preferred that the aqueous humor drainage device be implemented with a simple tubular structure, it will be appreciated that variations to such structures may be made. For example, other conduit forming structures and shapes may be used. In another example, the device may include a hole through a sidewall of the tubular structure. In another example, the tubular structure may include a plurality of lumens therein. Additionally, while it is preferred that the aqueous humor drainage device be implemented with a simple planar tab structure, it will be appreciated that variations to such structures may be made. Accordingly, it will be recognized by those skilled in the art that additional modifications may be made to the provided invention without departing from its spirit and scope as claimed.

Claims

1. An implantable device for treatment of elevated ocular pressure within the anterior chamber of an eye, the device comprising:

an elongated tube for transferring aqueous humor from the anterior chamber, the elongated tube having a central axis and proximal and distal ends opposite one another;

at least one element spaced from the proximal and distal ends of the elongate tube and extending radially outward beyond the outer surface of the elongate tube in two opposite directions transverse to the central axis of the elongate tube, wherein the at least one element has a distal portion with a tapered profile facing the distal end of the elongate tube, and wherein the at least one element has a maximum cross-sectional dimension defined by at least one blunt surface.

2. The apparatus of claim 1, wherein:

the at least one element has a circular cross-section in a direction transverse to the central axis of the elongated pipe; or

Said at least one element having a diamond shaped cross-section in a direction transverse to the central axis of said elongated conduit; or

Said at least one element having a rectangular cross-section in a direction transverse to the central axis of said elongated conduit; or

The at least one element has an elliptical cross-section in a direction transverse to a central axis of the elongated conduit.

3. The apparatus of claim 1, wherein:

the at least one element and the elongated conduit have different hardnesses.

4. The apparatus of claim 1, wherein:

the at least one element is configured to deform in response to a force applied by surrounding ocular tissue.

5. The apparatus of claim 1, wherein:

the at least one element includes first and second tabs extending radially beyond an outer surface of the elongated tube on opposite sides of the elongated tube, wherein the first and second tabs each have a distal surface with a tapered profile facing a distal end of the elongated tube.

6. The apparatus of claim 5, wherein:

the first tab and the second tab have a different durometer than the elongated tube.

7. The apparatus of claim 5, wherein:

the first tab and the second tab are configured to deform in response to a force applied by surrounding ocular tissue.

8. The apparatus of claim 5, wherein:

the first tab and the second tab each have a hardness in a range between 30 Shore A and 80 Shore A.

9. The apparatus of claim 5, wherein:

the first tab defines a first blunt outer surface;

the second tab defines a second blunt outer surface; and

the maximum cross-sectional dimension is defined by the maximum distance between the first blunt outer surface and the second blunt outer surface.

10. The apparatus of claim 1, wherein:

the elongated pipe has a maximum cross-sectional size of no greater than 0.4 mm; and

the maximum cross-sectional dimension defined by the at least one blunt surface of the at least one element is at least 0.9 mm.

11. The apparatus of claim 1, wherein:

the elongated tube has a proximal portion defining a cylindrical outer surface and a distal portion defining a cylindrical outer surface; and

the at least one element includes first and second tabs disposed intermediate the cylindrical outer surfaces of the proximal and distal portions of the elongate conduit.

12. The apparatus of claim 11, wherein:

the first and second tabs are generally planar in form and extend radially outward in a common plane beyond the cylindrical outer surfaces of the proximal and distal portions of the elongate conduit, and have respective tapered distal surfaces facing the distal end of the elongate conduit.

13. The apparatus of claim 11, wherein:

the first tab defines a first blunt outer surface and the second tab defines a second blunt outer surface, wherein the maximum cross-sectional dimension is defined by a maximum distance between the first and second blunt outer surfaces.

14. The apparatus of claim 1, wherein:

the device is an integrally molded part realized from a polymeric material selected from the group consisting of: SIBS materials, silicone rubbers, polyolefin polymers, polyurethane polymers, acrylic polymers, fluoropolymers, polyamide polymers, hydrogel polymers, bio-based structures, soft polymer foams, porous polymer materials, and combinations thereof.

15. The apparatus of claim 14, wherein:

the polymeric material used for at least a portion of the device is loaded with at least one therapeutic agent.

16. A kit for surgical treatment of elevated ocular pressure within an anterior chamber of an eye, the kit comprising:

a device having a needle for insertion through tissue to define a passageway connected to the anterior chamber, wherein the needle has a first maximum cross-sectional dimension along its length; and

an aqueous humor drainage device comprising an elongate tube and at least one element spaced from proximal and distal ends of the elongate tube, wherein the elongate tube is for transferring aqueous humor from the anterior chamber and has a central axis and proximal and distal ends opposite one another, and wherein the at least one element extends radially outward beyond an outer surface of the elongate tube in two opposite directions transverse to the central axis of the elongate tube, wherein the at least one element has a distal portion with a tapered profile facing the distal end of the elongate tube, and wherein the at least one element has a second maximum cross-sectional dimension defined by at least one blunt surface;

wherein the second maximum cross-sectional size is greater than the first maximum cross-sectional size so as to form a seal between the tissue and the at least one blunt surface of the at least one element.

17. The kit of claim 16, wherein:

18. The kit of claim 16, wherein:

the at least one element and the elongated conduit have different hardnesses.

19. The kit of claim 16, wherein:

20. The kit of claim 16, wherein:

21. The kit of claim 20, wherein:

22. The kit of claim 20, wherein:

23. The kit of claim 20, wherein:

24. The kit of claim 20, wherein:

the first tab defines a first blunt outer surface;

the second tab defines a second blunt outer surface; and

the second maximum cross-sectional dimension is defined by a maximum distance between the first blunt outer surface and the second blunt outer surface.

25. The kit of claim 16, wherein:

the first maximum cross-sectional size is in a range between 0.4mm and 0.7 mm; and

the second maximum cross-sectional dimension is at least 0.9 mm.

26. The kit of claim 16, wherein:

27. The kit of claim 26, wherein:

28. The kit of claim 26, wherein:

the first tab defines a first blunt outer surface and the second tab defines a second blunt outer surface, wherein the second maximum cross-sectional dimension is defined by a maximum distance between the first and second blunt outer surfaces.

29. The kit of claim 16, wherein:

the aqueous humor drainage device is an integrally molded part realized from a polymeric material selected from the group consisting of: SIBS materials, silicone rubbers, polyolefin polymers, polyurethane polymers, acrylic polymers, fluoropolymers, polyamide polymers, hydrogel polymers, bio-based structures, soft polymer foams, porous polymer materials, and combinations thereof.

30. The kit of claim 29, wherein:

31. The kit of claim 16, further comprising:

apparatus comprising a catheter dimensioned to receive the elongate tube of the aqueous humor drainage device, the catheter having a slot allowing the elongate tube of the aqueous humor drainage device to pass therethrough.

32. The kit of claim 31, wherein:

the notch extends along a portion of the catheter, wherein a tab is disposed near a proximal end of the notch for positioning the catheter.

33. The kit of claim 16, further comprising:

a stylet sized for insertion into an elongated tube of the aqueous humor drainage device.

34. The kit of claim 16, wherein:

the needle body of the instrument has a curved configuration.

35. The kit of claim 16, wherein:

the needle body of the instrument has a flat blade portion with two opposing cutting surfaces.